The invention is related to the field of Continuous Low Irradiance Photodynamic Therapy (CLIPT), and in particular to an implantable CLIPT illumination system.
Photodynamic Therapy (PDT) is a two-step, drug-device combination therapy that uses specific wavelengths of light to activate photosensitive drugs to kill cancer cells. Widespread adoption of PDT as a form of cancer treatment has been limited by a number of factors, most notably excessive morbidity, lack of penetration of the energy and the complexity of administering the therapy. CLIPT was introduced as a new therapeutic paradigm to reduce these standard PDT limitations and side-effects by delivering light at ultra-low dose-rates (0.1-0.5 mW) over a period of hours to days compared to traditional PDT delivered at a high dose-rate (2-5 W) occurring over a period of seconds to minutes. In recent clinical studies of 15 patients under a Susan G. Komen for the Cure® Foundation grant (Komen Study) and a NIH SBIR Phase I grant (NIH SBIR Study), CLIPT has shown >80% tumor response, as evidence by tumor shrinkage and or apoptosis at a depth well beyond conventional PDT. The side effects were minimal edema and eccymoses, no necrosis, and no full thickness ulcerations of normal tissues as often occur with standard radiation and conventional PDT.
The CLIPT 2nd Gen (light delivery device) LDD includes the development of the Light Diffusion Technology (LDT) manufacturing process that enables light emission from the LDD surface in a highly controllable, uniform and scalable manner. The 1st Gen LDD utilizing Lumitex's technology was a weaved collection of fiber optic cables that were bent sharply at several locations along the length of the fiber. The bending of the fiber causes light to leak from the fiber illuminating a small portion of a light illumination surface that consists of hundreds to thousands of these bent fibers spread across 7 layers of fiber optic material. This weaved fiber approach provides imprecise quantities of light at the treatment site because the bending (the mechanism of light leakage) of the fiber is not uniform from bend to bend and the location of bending along similarly aligned fibers can be random from fiber to fiber. The 1st Gen LDD exhibited irradiance uniformity performance of −37%/+28% across the 10 cm×10 cm area of the device. Not only is the light uniform inconsistent, the device is heavy, not flexible, has low optical efficiency, and is not scalable to larger areas.
In comparison, the LDT used on the 2nd Gen LDD uses a precision mounted and motorized laser scoring process that can be moved along the length of one or more fibers. The scoring process in general allows for light to exit the fiber by non-total-internal-reflection bending to create precision illumination along the entire length of the fiber based LDD. Irradiance repeatability of 2nd Gen LDD devices is within +/−2%, far below our target goal of +/−10% and far below the irradiance variability of the 1st Gen LDD. With precision laser etching of the fiber, it allows for predictable illumination along the length of one fiber in a linear or non-linear controlled output. Due to the etching process, similarly aligned fibers will have similar etching and performance such that an array of fibers can be stacked in a one-dimension, two-dimensional, or three-dimensional pattern for predictable and uniform illumination. Due to the simpler design and fabrication method, the overall thickness of the LDD pad (the 10 cm2 illumination surface) is 0.7 mm with a maximum working bend radius of 5 cm along the length (longitudinal) of the fiber LDD and 1 cm across (lateral) the LDD. The 1st Gen LDD had a thickness of 10 mm and a longitudinal bend radius of approximately 45 cm and a lateral bend radius of approximately 60 cm, significantly larger than that of the 2nd Gen LDD. In general the LDT process also significantly reduces the amount of fiber optic material required for the LDD, which results in significantly improved device mechanical properties, particularly body contour flexibility, as well as a lower cost to manufacture. Additionally, by utilizing the fiber in a more predictable manner optical efficiency increased from under 10% with the 1st Gen LDD to nearly 15% efficiency with the 2nd Gen LDD.
The second major innovation of the 2nd Gen LDD was the extension of this laser scoring technique to control the irradiance distribution pattern on the LDD surface. It has been demonstrated the ability to use this new manufacturing scoring technique to correct for laser mode patterns and achieve our irradiance uniformity specification. When using a laser source, the mode pattern of the laser beam is Gaussian which means the beam has its greatest intensity on center and the intensity falls off in intensity along the width of the beam with a Gaussian profile. Thus, illumination on the LDD emission surface was brighter in the middle and decreased in brightness towards the edges of the LDD. This was a problem with both the 1st Gen LDD woven architecture and with the new 2nd Gen LDD. Possible means for mode or Gaussian correction include diffusers, mode scrambling via pinching fibers, or moving fibers from the center of the LDD to the edges and some of the fibers from the edges to the center to smooth out the intensity across the LDD surface.